GB对脑梗死大鼠中NF-κB信号通路及血-脑脊液屏障的调节及作用研究

Regulation and effect of Ginkgolide B on NF-κB signaling pathway and blood-cerebrospinal fluid barrier in cerebral infarction rats

目的探讨银杏内酯B(GB)对脑梗死后炎症反应和血-脑脊液屏障(BCFB)的调节机制研究。方法采用线栓法建立大鼠永久性大脑中动脉闭塞模型。Sprague-Dawley(SD)大鼠随机分为4组:假手术组、溶剂对照组、和给药组(GB 15mg,30mg·kg^(-1))。术后24 h和72 h分别对大鼠进行神经症状评分,TTC染色法测定脑梗死范围,干湿重法测定脑组织含水量,评估神经功能障碍和损伤程度,TTC染色法测定脑梗死体积。并分别采用Western blot、RT-PCR及免疫组织化学方法、观察缺血周围区(NF-κB)和Claudin-5表达的变化。结果GB 30mg·kg^(-1)能改善大鼠缺血后神经症状评分、减少梗死范围、减轻脑水肿,Western blot、RT-PCR及免疫组织化学显示GB 30mg·kg^(-1)可降低脑缺血后大脑皮质NF-κB表达,促进Claudin-5表达量的升高。结论大剂量GB对局灶性脑缺血具有神经保护的作用。其保护作用可能与上调Claudin-5和下调NF-κB表达有关。

Objective To investigate the regulation mechanism of Ginkgolide B on inflammatory response and blood-cerebrospinal fluid barrier(BCFB) after cerebral infarction.Methods The permanent model of middle cerebral artery occlusion(MCAO) in rats was established by suture plug method.Sprague-Dawley(SD) rats were randomly divided into 4 groups:sham operation group,vehicle group and treatment group(Ginkgolide B 15 mg,30 mg·kg^(-1)).To assess the degree of neurological dysfunction and damage,the neuropathy symptom score,dry and wet weight method and TTC staining was used to determine the extent of cerebral infarction at 24 h and 72 h after postoperratively.The expression of NF-kappaB inhibitor alpha(NF-κB) and Claudin-5 was observed by immunohistochemistry,Western blot and RT-PCR in the ischemic area at 24 h and 72 h after surgery.Results Ginkgolide B 30 mg·kg^(-1)can improve neurological function score,reduce infarct volume and relieve cerebral edema after ischemia in rats.Western blot RTPCR and immunohistochemistry,showed that Ginkgolide B 30 mg·kg;could decrease the expression of NF-κB and promote the expression of Claudin-5 after ischemia.Conclusion High dose Ginkgolide B has neuroprotective effect on focal cerebral ischemia.The protective effect may be related to up-regulation of Claudin-5 and down-regulation of NF-κB expression.